The incidence of steroidogenic blocks in Clomiphene Citrate-resistant PCOS patients and in normal ovulatory controls J.G. Dolfing, D.H. Schweitzer, K.E. Tucker and C.A.M. Jansen Department of IVF and Endocrinology, Reinier de Graaf Groep, Diaconessenhuis Voorburg, The Netherlands

Patients and Methods 26 primary infertile PCOS patients CC-resistant up to 150 mg Fasting insulin, glucose, LH, FSH, estradiol, androstenedione, total testosterone, SHBG, Free Testosterone Index, steroid-precursors 12 ovulatory healthy volunteers After 5x3mg dexamethasone: total testosterone, FTI, cortisol, steroid-precursors After ACTH-stimulation steroid-precursors

1 17OH pregnenolone Compound-S cortisol 17OH progesterone 3ß-hydroxy  5 -steroid dehydrogenase 21-  hydroxylase 11-  hydroxylase Methods Steroid-precursors at baseline and after 250µg ACTH:

Results demographic and endocrine determinations

Results Steroid-precursors at baseline and after ACTH-stimulation

stimulated 17-OH progesterone/compound-s controls patients baseline

stimulated compound-s/cortisol controls patients baseline

stimulated 17-OH pregnenolone/17- OH progesterone controls patients baseline

Correlations linear regression analysis base-lineafter dexamethasone Rp-valueRp-value BMI - insulin0.74 < BMI - testosterone BMI- FTI No correlation between precursor-to-product ratios, insulin or BMI

hyper- testosteronaemia hyperinsulinaemia Steroid- precursor abnormality Clomiphene-resistant patients Conclusion

Results Precursor-to-product ratios at baseline and after ACTH-stimulation

1 cholesterol pregnenolone DOC corticosterone aldost. 17OH pregnenolone DHEA androstenediole 11-DOC cortisol 11OH- androstenedione oestrone oestradioledihydrotestosterone DHEAS Steroidogenesis progesterone 17OH progesterone testosterone androstenedione

Effekt insulin Thecacel LH Androgens insulin IGF I P450c-17  IGF-BP SHBG FSH Granulosa cel atresie